Abstract:Malaria remains a significant disease, causing epic health problems and challenges all over the world, especially in sub-Saharan Africa. CD209 and CD28 genes act as co-stimulators and regulators of the immune system, while the STAT6 gene has been reported to mediate cytokine-induced responses. Single nucleotide polymorphisms of these genes might lead to differential disease susceptibility among populations at risk for malaria, due to alterations in the immune response. We aim to identify key drivers of the imm… Show more
“…Although polymorphisms located in the promoter region of CD209 are widely associated with the severity of various infectious diseases, (31,32,44,50,51) including tuberculosis, (30) such association has not yet been reported in leprosy. In view of the relevance of DC-SIGN in the recognition of antigens and activation of the immune response, and considering that the variations in genes that potentially influence the course of infections are largely population-dependent (52) we chose to investigate the association of candidate variants in the CD209 promoter region with the clinical manifestation of leprosy in a Brazilian population.…”
BACKGROUND Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation.OBJECTIVES To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects.
METHODSThe study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed.
RESULTSThe GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-β1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test.CONCLUSION These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.
“…Although polymorphisms located in the promoter region of CD209 are widely associated with the severity of various infectious diseases, (31,32,44,50,51) including tuberculosis, (30) such association has not yet been reported in leprosy. In view of the relevance of DC-SIGN in the recognition of antigens and activation of the immune response, and considering that the variations in genes that potentially influence the course of infections are largely population-dependent (52) we chose to investigate the association of candidate variants in the CD209 promoter region with the clinical manifestation of leprosy in a Brazilian population.…”
BACKGROUND Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation.OBJECTIVES To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects.
METHODSThe study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed.
RESULTSThe GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-β1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test.CONCLUSION These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.
“…Additionally, in an experimental model with an advanced fibrosis resembling advanced hepatic fibrosis from human schistosomiasis, a role of Th17 response is demonstrated, whereas in human schistosomiasis, there is no clear understanding of what occurs in the later stages of fibrosis (9). Furthermore, the genetic background of the host might be involved in the modulation of immune response and pathogenesis development, as seen in many infectious diseases (10)(11)(12)(13)(14)(15). Thus, functional single nucleotide polymorphisms (SNPs) may be important as they may influence the gene expression or the structure of the corresponding protein (16).…”
This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP—10 μg/ml) or egg (SEA—10 μg/ml) antigens or purified protein derivative of turberculin (PPD—10 μg/ml) or phytohemagglutinin (PHA—1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.
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